FILMARRAY RESPIRATORY PANEL (RP)
Device Facts
| Record ID | K123620 |
|---|---|
| Device Name | FILMARRAY RESPIRATORY PANEL (RP) |
| Applicant | Biofire Diagnostics, Inc. |
| Product Code | OCC · Microbiology |
| Decision Date | Feb 11, 2013 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 866.3980 |
| Device Class | Class 2 |
Intended Use
FilmArray® Respiratory Panel (RP) is a multiplexed nucleic acid test intended for use with the FilmArray Instrument for the simultaneous qualitative detection and identification of multiple respiratory viral and bacterial nucleic acids in nasopharyngeal swabs (NPS) obtained from individuals suspected of respiratory tract infections. The following organism types and subtypes are identified using the FilmArray RP: Adenovirus, Coronavirus 229E, Coronavirus HKU1, Coronavirus NL63, Coronavirus OC43, Human Metapneumovirus, Influenza A, Influenza A subtype H1, Influenza A subtype H3, Influenza A subtype H1-2009, Influenza B, Parainfluenza Virus 1, Parainfluenza Virus 2, Parainfluenza Virus 3, Parainfluenza Virus 4, Human Rhinovirus/Enterovirus, Respiratory Syncytial Virus, Bordetella pertussis, Chlamydophila pneumoniae, and Mycoplasma pneumoniae. The detection and identification of specific viral and bacterial nucleic acids from individuals exhibiting signs and symptoms of a respiratory infection aids in the diagnosis of respiratory infection if used in conjunction with other clinical and epidemiological information. The results of this test should not be used as the sole basis for diagnosis, treatment, or other management decisions. Negative results in the setting of a respiratory illness may be due to infection with pathogens that are not detected by this test or, lower respiratory tract infection that is not detected by a nasopharyngeal swab specimen. Positive results do not rule out co-infection with other organisms: the agent(s) detected by the FilmArray RP may not be the definite cause of disease. Additional laboratory testing (e.g. bacterial and viral culture, immunofluorescence, and radiography) may be necessary when evaluating a patient with possible respiratory tract infection.
Device Story
FilmArray RP system performs multiplexed nucleic acid testing on nasopharyngeal swab samples. System comprises FilmArray instrument, preinstalled software, and single-use reagent pouch. User loads sample and hydration solution into pouch; instrument automates nucleic acid extraction, purification, and nested multiplex RT-PCR. First stage performs large-volume multiplexed RT-PCR; second stage performs singleplex nested PCR in array wells using fluorescent DNA binding dye. Digital camera captures real-time fluorescent images during DNA melt analysis. Software automatically interprets melt curves to identify 20 respiratory pathogens. Results provided to clinician to aid diagnosis of respiratory infections in conjunction with other clinical data. Benefits include rapid (approx. 1 hour) identification of multiple pathogens, facilitating timely clinical management.
Clinical Evidence
Clinical comparison study using 222 archived nasopharyngeal swab specimens and 44 contrived specimens. Primary endpoint: positive/negative percent agreement between original and modified FilmArray RP. Modified panel showed 73% greater detection rate for Adenovirus in archived samples. Adenovirus PPA 100% (15/15), NPA 94.7% (196/207). Contrived specimen testing confirmed improved detection of Adenovirus serotypes C2 and C6. Performance for other 19 analytes remained equivalent. Discrepant results investigated via bi-directional sequence analysis; low viral load suspected for most discrepancies.
Technological Characteristics
Multiplex nucleic acid test system. Materials: freeze-dried reagents in single-use pouch. Sensing: nested multiplex RT-PCR with high-resolution DNA melt analysis using LC Green®Plus dye. Energy: Peltier devices for thermal cycling. Connectivity: standalone instrument with laptop-based software. Automated sample preparation via mechanical lysis and magnetic beads. Software: automated interpretation of melt curves.
Indications for Use
Indicated for individuals suspected of respiratory tract infections exhibiting signs and symptoms of respiratory infection. Used for qualitative detection and identification of multiple respiratory viral and bacterial nucleic acids in nasopharyngeal swabs.
Regulatory Classification
Identification
A respiratory viral panel multiplex nucleic acid assay is a qualitative in vitro diagnostic device intended to simultaneously detect and identify multiple viral nucleic acids extracted from human respiratory specimens or viral culture. The detection and identification of a specific viral nucleic acid from individuals exhibiting signs and symptoms of respiratory infection aids in the diagnosis of respiratory viral infection when used in conjunction with other clinical and laboratory findings. The device is intended for detection and identification of a combination of the following viruses:(1) Influenza A and Influenza B; (2) Influenza A subtype H1 and Influenza A subtype H3; (3) Respiratory Syncytial Virus subtype A and Respiratory Syncytial Virus subtype B; (4) Parainfluenza 1, Parainfluenza 2, and Parainfluenza 3 virus; (5) Human Metapneumovirus; (6) Rhinovirus; and (7) Adenovirus.
Special Controls
*Classification.* Class II (special controls). The special controls are:(1) FDA's guidance document entitled “Class II Special Controls Guidance Document: Respiratory Viral Panel Multiplex Nucleic Acid Assay;” (2) For a device that detects and identifies Human Metapneumovirus, FDA's guidance document entitled “Class II Special Controls Guidance Document: Testing for Human Metapneumovirus (hMPV) Using Nucleic Acid Assays;” and (3) For a device that detects and differentiates Influenza A subtype H1 and subtype H3, FDA's guidance document entitled “Class II Special Controls Guidance Document: Testing for Detection and Differentiation of Influenza A Virus Subtypes Using Multiplex Nucleic Acid Assays.” See § 866.1(e) for the availability of these guidance documents.
Predicate Devices
- FilmArray Respiratory Panel (RP) (K103175, K110764 and K120267)
Related Devices
- K120267 — FILMARRAY RP PANEL · Idaho Technology, Inc. · May 15, 2012
- K160068 — FilmArray Respiratory Panel (RP) for use with FilmArray Torch · Biofire Diagnostics, LLC · Feb 8, 2016
- K110764 — FILMARRAY RP PANEL · Idaho Technology, Inc. · Apr 27, 2011
- K152579 — FilmArray Respiratory Panel EZ (RP EZ) · Biofire Diagnostics, LLC · Oct 3, 2016
- K143080 — FilmArray Respiratory Panel (RP) for use with Multi-instrument FilmArray System · Biofire Diagnostics, LLC · Feb 17, 2015
Submission Summary (Full Text)
{0}------------------------------------------------
K123620
# 510(k) Summary
FEB 1 1 2013
# Modification of FilmArrav® Respiratorv Panel (RP) to add an additional assay to detect Adenovirus .
Introduction: According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence.
#### Submitted by:
BioFire Diagnostics, Inc. 390 Wakara Way Salt Lake City, UT 84108
Telephone: 801-736-6354 Facsimile: 801-588-0507
Contact: Beth Lingenfelter, ext. 407
Date Submitted: November 21, 2012
#### Device Name and Classification:
Trade Name: FilmArray® Respiratory Panel (RP)
Regulation Number: 21 CFR 866.3980
Classification Name: Respiratory Viral Panel Multiplex Nucleic Acid Assay
### Predicate Device:
FilmArray Respiratory Panel (RP) (K103175, K110764 and K120267)
### Intended Use:
FilmArray® Respiratory Panel (RP) is a multiplexed nucleic acid test intended for use with the FilmArray Instrument for the simultaneous qualitative detection and identification of multiple respiratory viral and bacterial nucleic acids in nasopharyngeal swabs (NPS) obtained from individuals suspected of respiratory tract infections. The following organism types and subtypes are identified using the FilmArray RP: Adenovirus, Coronavirus 229E, Coronavirus HKU1, Coronavirus NL63, Coronavirus OC43, Human Metapneumovirus, Influenza A, Influenza A subtype H1, Influenza A subtype H3, Influenza A subtype H1-2009, Influenza B, Parainfluenza Virus 1, Parainfluenza Virus 2, Parainfluenza Virus 3, Parainfluenza Virus 4, Human
{1}------------------------------------------------
Rhinovirus/Enterovirus, Respiratory Syncytial Virus, Bordetella pertussis, Chlamydophila pneumoniae, and Mycoplasma pneumoniae. The detection and identification of specific viral and bacterial nucleic acids from individuals exhibiting signs and symptoms of a respiratory infection aids in the diagnosis of respiratory infection if used in conjunction with other clinical and epidemiological information. The results of this test should not be used as the sole basis for diagnosis, treatment, or other management decisions. Negative results in the setting of a respiratory illness may be due to infection with pathogens that are not detected by this test or, lower respiratory tract infection that is not detected by a nasopharyngeal swab specimen. Positive results do not rule out co-infection with other organisms: the agent(s) detected by the Film Array RP may not be the definite cause of disease. Additional laboratory testing (e.g. bacterial and viral culture, immunofluorescence, and radiography) may be necessary when evaluating a patient with possible respiratory tract infection.
Due to the small number of positive specimens collected for certain organisms during the prospective clinical study, performance characteristics for Bordetella pertussis, Coronavirus 229E, Coronavirus OC43, Influenza A H1, Influenza A H3, Influenza A H1-2009, Influenza B, Mycoplasma pneumoniae, Parainfluenza Virus 1, Parainfluenza Virus 2, and Parainfluenza Virus 4 were established primarily with retrospective clinical specimens. Performance characteristics for Chlamydophila pneumoniae were established primarily using contrived clinical specimens.
Due to the genetic similarity between Human Rhinovirus and Enterovirus, the FilmArray RP cannot reliably differentiate them. A positive FilmArray RP Rhinovirus/Enterovirus result should be followed-up using an alternate method (e.g., cell culture or sequence analysis).
The FilmArrav RP assay for Coronavirus OC43 may cross-react with some isolates of Coronavirus HKU1. A dual positive result may be due to cross-reactivity or may indicate a co-infection.
Performance characteristics for Influenza A were established when Influenza A H1-2009. A H1, and A H3 were the predominant Influenza A viruses in circulation. Performance of detecting Influenza A may vary if other Influenza A strains are circulating or a novel Influenza A virus emerges. If infection with a novel Influenza A virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent Influenza viruses and sent to state or local health departments for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.
#### Device Description:
The FilmArray RP System is a multiplex nucleic acid test system composed of the FilmArray instrument, the FilmArray software (preinstalled on a laptop computer) and the FilmArray RP pouch. The FilmArray RP reagent pouch contains freeze-dried reagents
{2}------------------------------------------------
to perform nucleic acid purification, reverse transcription, and nested, multiplex PCR with DNA melt analysis. The RP identifies 20 respiratory pathogens as shown in the following table.
| Viral Respiratory Pathogens |
|---------------------------------|
| Adenovirus |
| Coronavirus 229E |
| Coronavirus HKU1 |
| Coronavirus NL63 |
| Coronavirus OC43 |
| Human Metapneumovirus |
| Human Rhinovirus/Enterovirus |
| Influenza A |
| H1 subtype |
| H3 subtype |
| H1-2009 subtype |
| Influenza B |
| Parainfluenza Virus 1 |
| Parainfluenza Virus 2 |
| Parainfluenza Virus 3 |
| Parainfluenza Virus 4 |
| Respiratory Syncytial Virus |
| Bacterial Respiratory Pathogens |
| Bordetella pertussis |
| Chlamydophila pneumoniae |
| Mycoplasma pneumoniae |
Organisms Detected by the FilmArray Respiratory Panel
A test is initiated by loading Hydration Solution and an unprocessed patient nasopharyngeal swab (NPS) specimen (i.e., specimen mixed with Sample Buffer) into the FilmArray RP pouch. The pouch contains all of the reagents required for specimen testing and analysis in a freeze-dried format; the addition of Hydration Solution and specimen/Sample Buffer Mix rehydrates the reagents. After the pouch is prepared, the FilmArray software guides the user though the steps of placing the pouch into the instrument, scanning the pouch barcode, entering the sample identification, and initiating the run.
The FilmArray instrument contains a coordinated system of inflatable bladders and seal points, which act on the pouch to control the movement of liquid between the pouch blisters. When a bladder is inflated over a reagent blister, it forces liquid from the blister into connecting channels. Alternatively, when a seal is placed over a connecting channel it acts as a valve to open or close a channel. In addition, electronically controlled pneumatic pistons are positioned over multiple plungers in order to deliver the rehydrated reagents into the blisters at the appropriate times. Two Peltier devices control heating and cooling of the pouch to drive the reverse transcription reactions, the PCR reactions, and the melting curve analysis.
Nucleic acid extraction occurs within the FilmArray pouch using mechanical lysis and standard magnetic bead technology. After extracting and purifying nucleic acids from the
{3}------------------------------------------------
unprocessed sample, the FilmArray performs a nested multiplex PCR that is executed in two stages. During the first stage, the FilmArray performs a single, large volume, highly multiplexed reverse transcription PCR (rt-PCR) reaction. The products from first stage PCR are then diluted and combined with a fresh, primer-free master mix and a fluorescent double stranded DNA binding dye (LC Green®Plus, BioFire Diagnostics). This second master mix solution; is then distributed to each well of the array. Array wells contain sets of primers designed specifically to amplify sequences internal to the PCR products generated during the first stage PCR reaction. The second stage PCR, or nested PCR, is performed in singleplex fashion in each well of the array. At the conclusion of the 200 stage PCR, the array is interrogated by melting curve analysis for the detection of signature amplicons denoting the presence of specific viral or bacterial targets. A digital camera placed in front of the second stage PCR captures fluorescent images of the PCR reactions in real time.
The FilmArray software automatically interprets the results of each DNA melting curve analysis and combines the data with the results of the internal pouch controls to provide a test result for each organism on the panel.
# Substantial Equivalence:
The FilmArray RP is substantially equivalent to previously cleared FilmArray RP versions. The following tables compare the modified FilmArray RP to the previously cleared FilmArray RP (K103175, K110764 and K120267). The first table outlines the similarities between the two systems and the following table outlines the differences.
| Element | New Device:<br>FilmArray Respiratory Panel | Predicate:<br>FilmArray Respiratory Panel<br>(K103175, K110764 and K120267) |
|-----------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------|
| Organisms<br>Detected | Influenza A, Influenza A subtype H1,<br>Influenza A subtype H3, Influenza A<br>subtype H1-2009 Influenza B, Respiratory<br>Syncytial Virus, Human Metapneumovirus,<br>Adenovirus, Parainfluenza 1, Parainfluenza<br>2, Parainfluenza virus 3, Parainfluenza 4,<br>Rhinovirus/Enterovirus, Coronavirus<br>HKU1, Coronavirus NL63, Coronavirus<br>229E, Coronavirus OC43, Mycoplasma<br>pneumoniae, Chlamydophila pneumoniae,<br>and Bordetella pertussis. | Same |
| Analyte | RNA/DNA | Same |
| Technological<br>Principles | Multiplex nucleic acid | Same |
| Specimen Types | Nasopharyngeal swabs | Same |
#### Similarities between the Modified Device and the Predicate.
{4}------------------------------------------------
| Technological<br>Principles | Nested multiplex RT-PCR followed by high<br>resolution melting analysis to confirm<br>identity of amplified product. | Same |
|---------------------------------|----------------------------------------------------------------------------------------------------------------------------------|------|
| Instrumentation | FilmArray Instrument | Same |
| Time to result | About 1 hour | Same |
| Test<br>Interpretation | Automated test interpretation and report<br>generation. User cannot access raw data. | Same |
| Sample<br>Preparation<br>Method | Sample Processing is automated in the<br>FilmArray RP pouch. | Same |
| Reagent Storage | Reagents are stored at room temperature. | Same |
| Controls | Two controls are included in each reagent<br>pouch to control for sample processing and<br>both stages of PCR and melt analysis. | Same |
| User<br>Complexity | Moderate/Low | Same |
# Differences between the Modified Device and the Predicate.
.
:
.
. Carlos Career States
1000
| Element | Modified Device:<br>FilmArray Respiratory Panel | Predicate:<br>FilmArray Respiratory Panel<br>(K103175, K110764 and K120267) |
|-----------------------------------------|-------------------------------------------------|-------------------------------------------------------------------------------------|
| Limit of<br>Detection for<br>Adenovirus | 100 TCID50/mL | 300 TCID50/mL |
| Detection of<br>Adenovirus<br>Serotypes | Detects all serotypes with similar sensitivity | Detects Adenovirus species C serotype 2<br>and serotype 6 with reduced sensitivity. |
.
:
:
:
・
.
・
{5}------------------------------------------------
# Summary of Performance Data
# Clinical Comparison
The original FilmArray RP was modified by the addition of a second Adenovirus assay. To demonstrate the performance of the modified FilmArray RP, a comparison study was performed by testing 222 de-identified archived nasopharyngeal swab (NPS) specimens collected between 2008 and 2011 throughout the United States (at least 8 geographically distinct locations) and Scotland (at least 1 location) with both the original FilmArray RP and the modified FilmArray RP. A total of 26 Adenovirus specimens were detected by the modified FilmArray RP, of these only 15 were detected by the original FilmArray RP, demonstrating a 73% greater detection rate by the modified FilmArray RP in this clinical comparison study. For the other 19 analytes on the panel, performance appeared to be equivalent between the original and modified FilmArray RP versions.
| | Positive Agreement | | | | Negative Agreement | | | |
|------------------|-----------------------------------------|-----------------------------------------|------------------|--------------|--------------------|-----------------------------------------|--------------------|--------------|
| Analyte | orig<br>+ mod + | orig<br>+ mod - | PPA | 95% CI | orig -<br>mod - | orig<br>+ mod + | NPA | 95% CI |
| Adenovirus | 15 | 0 | 100%<br>(15/15) | 78.2 - 100% | 196 | 11 a | 94.7%<br>(196/207) | 90.7 – 97.3% |
| CoV 229E | 6 | 0 | 100%<br>(6/6) | 54.1 - 100% | 216 | 0 | 100%<br>(216/216) | 98.3 - 100% |
| CoV HKU1 | 8 | 0 | 100%<br>(8/8) | 63.1 - 100% | 214 | 0 | 100%<br>(214/214) | 98.3 - 100% |
| CoV NL63 | 15 | 1 b | 93.8%<br>(15/16) | 69.8 - 99.8% | 206 | 0 | 100%<br>(206/206) | 98.2 - 100% |
| CoV OC43 | 13 | 0 | 100%<br>(13/13) | 75.3 - 100% | 208 | 1 c | 99.5%<br>(208/209) | 97.4- 100% |
| hMPV | 10 | 0 | 100%<br>(10/10) | 69.2 - 100% | 209 | 3 d | 98.6%<br>(209/212) | 95.9 - 99.7% |
| HRV/EV | 57 | 4 e | 93.4%<br>(57/61) | 84.0 - 98.2% | 158 | 3 e | 98.1%<br>(158/161) | 94.6 - 99.6% |
| Flu A | 36 | 0 | 100%<br>(36/36) | 90.3 - 100% | 184 | 1 f | 99.5%<br>(184/185) | 97.0-100% |
| Flu A H1 | 9 | 0 | 100%<br>(9/9) | 66.4 - 100% | 213 | 0 | 100%<br>(213/213) | 98.3 - 100% |
| Flu A H1<br>2009 | 15 | 0 | 100%<br>(15/15) | 78.2 - 100% | 205 | 1 f | 99.5%<br>(205/206) | 97.3 - 100% |
| Flu A H3 | 13 | 0 | 100%<br>(13/13) | 75.3 - 100% | 209 | 0 | 100%<br>(209/209) | 98.3 - 100% |
| Flu B | 10 | 0 | 100%<br>(10/10) | 69.2 - 100% | 212 | 0 | 100%<br>(212/212) | 98.3 - 100% |
| RSV | 21 | 0 | 100%<br>(21/21) | 83.9 - 100% | 201 | 0 | 100%<br>(201/201) | 98.2 - 100% |
| PIV1 | 11 | 0 | 100%<br>(11/11) | 71.5 - 100% | 211 | 0 | 100%<br>(211/211) | 98.3 - 100% |
Performance Comparison of Modified FilmArray RP to Original FilmArray RP using Archived Specimens
6 | P a g e
{6}------------------------------------------------
| | Positive Agreement | | | Negative Agreement | | | | |
|--------------------------|-----------------------|-----------------------|------------------|--------------------|-----------------|-----------------------|--------------------|--------------|
| Analyte | orig<br>+<br>mod<br>+ | orig<br>+<br>mod<br>- | PPA | 95% CI | orig -<br>mod - | orig<br>-<br>mod<br>+ | NPA | 95% CI |
| PIV2 | 8 | 0 | 100%<br>(8/8) | 63.1 - 100% | 214 | 0 | 100%<br>(214/214) | 98.3 - 100% |
| PIV3 | 18 | 0 | 100%<br>(18/18) | 81.5 - 100% | 204 | 0 | 100%<br>(204/204) | 98.2 - 100% |
| PIV4 | 6 | 0 | 100%<br>(6/6) | 54.1 - 100% | 214 | 2 | 99.1%<br>(214/216) | 96.7 - 99.9% |
| <i>B. pertussis</i> | 25 | 1h | 96.2%<br>(25/26) | 80.4 - 99.9% | 196 | 0 | 100%<br>(196/196) | 98.1 - 100% |
| <i>C.<br/>pneumoniae</i> | 1 | 0 | 100%<br>(1/1) | n/a | 221 | 0 | 100%<br>(221/221) | 98.3 - 100% |
| <i>M.<br/>pneumoniae</i> | 0 | 0 | n/a | n/a | 222 | 0 | 100%<br>(222/222) | 98.4 - 100% |
orig = original FilmArray RP, mod = modified FilmArray RP, PPA = positive percent agreement, NPA = negative percent agreement, CI = confidence interval
4 10/11 of the additional AdV detections by the modified FilmArray RP were confirmed to contain Adenovirus by bidirectional sequence analysis; these Adenoviruses were identified by sequencing as serotypes C2, C5, C6, E4, and one undetermined serotype. One specimen could not be sequenced due to low analyte levels.
o A single specimen was found to be positive for CoV NL63 when tested with the original RP pouch but not the modified RP pouch. The specimen had previously been identified as positive for B. pertussis and had not been tested for CoV NL63 by the source laboratory. This specimen previously tested using the original pouch was negative for CoV NL63 . There was insufficient specimen for discrepancy investigation. Low viral load is suspected to have caused this spurious result.
6 The Coronavirus OC43 discrepancy was due to cross-reactivity between the OC43 assay and HKU1 virus that was detected in the RP modified pouch and not in the original RP pouch.
4 2/3 human Metapneumovirus discrepant specimens were confirmed by bi-directional sequence analysis. Low viral load is suspected to have prevented detection by sequencing for the other specimen.
\$ 0/7 Human Rhinovirus/Enterovirus discrepant specimens were confirmed by bi-directional sequence analysis. Low viral load is suspected to have prevented detection by sequencing .
A single specimen containing Influenza A H1-2009 provided results on the original RP pouch, but was detected by the modified pouch.
8 Parainfluenza Virus 4 was confirmed in both discrepant specimens by bi-directional sequence analysis.
B. pertussis was confirmed in the discrepant specimen by bi-directional sequence analysis.
To supplement the archived specimen data for low prevalence analytes and to provide additional Adenovirus performance data specifically for serotypes C2 and C6, a set of 44 contrived (spiked NPS) specimens (10 AdVC2, 10 AdVC6, 10 C. pneumoniae, and 14 M. pneumoniae) was tested with both the modified FilmArray RP and the original FilmArray RP. The analyte status of each contrived specimen was blinded to the users analyzing the specimens. The modified FilmArray RP detected all 20 Adenovirus-spiked specimens, while the original FilmArray RP detected none of the Adenovirus-spiked specimens. The modified FilmArray RP also detected another Adenovirus in the background of a specimen spiked with C. pneumoniae. Performance appeared to be equivalent between the modified FilmArray RP and the original FilmArray RP for C. pneumoniae and M. pneumoniae.
{7}------------------------------------------------
| Analyte | Positive Agreement | | | | Negative Agreement | | | |
|--------------------------------|--------------------|-----------------|-----------------|-----------------|--------------------|-----------------|------------------|-----------------|
| | orig +<br>mod + | orig +<br>mod - | PPA | 95% CI | orig -<br>mod - | orig -<br>mod + | NPA | 95% CI |
| Adenovirus<br>(C2 and C6) | 0 | 0 | n/a | n/a | 23 | 21a | 52.3%<br>(23/44) | 36.7 –<br>67.5% |
| <i>C.</i><br><i>pneumoniae</i> | 8 | 1 | 88.9%<br>(8/9) | 51.8 –<br>99.7% | 35 | 0 | 100%<br>(35/35) | 90.0 – 100% |
| <i>M.</i><br><i>pneumoniae</i> | 14 | 0 | 100%<br>(14/14) | 76.8 – 100% | 30 | 0 | 100%<br>(30/30) | 88.4 – 100% |
Clinical Comparison Data of Modified FilmArray RP to Original FilmArray RP for 44 Contrived Specimens
orig = original FilmArray RP, mod = modified FilmArray RP, PPA = positive percent agreement, NPA = negative percent agreement, CI = confidence interval
4 In addition to ten specimens spiked with Adenovirus C6 and ten specimens spiked with Adenovirus C2, the modified FilmArray RP also detected an Adenovirus in the background of one speciment that had been spiked with C. pneumoniae. This detection was confirmed by bi-directional sequence analysis to be Adenovirus C2.
The Adenoviruses detected in archived specimens were categorized into serotype groups using bi-directional sequence analysis. Combining the archived specimen comparison data demonstrates improved detection of serotypes C2, C5, C6 and E4 by the modified FilmArray RP.as compared to the original FilmArray RP.
Adenovirus Serotype Detections by the Modified Film Array RP and the Original FilmArray RP in Archived and Contrived Specimens
| Adenovirus<br>(Serotyped by PCR) | Number of Adenovirus-<br>positive Specimens<br>(as Detected by Modified<br>FilmArray RP) | Detections by Original<br>FilmArray RP |
|----------------------------------|------------------------------------------------------------------------------------------|----------------------------------------|
| AdVC1 | 8 | 8/8 (100%) |
| AdVC2 | 15a | 2/15 (13%) |
| AdVC5 | 2 | 1/2 (50%) |
| AdVC6 | 16a | 1/16 (6%) |
| AdVB3 | 1 | 1/1 (100%) |
| AdVE4 | 3 | 2/3 (67%) |
| AdV serotype unknown | 2 | 0/2 (0%) |
4 Ten C2 specimens and ten C6 specimens were contrived by spiking these viruses into NPS specimens. One C2 was also detected and sequence confirmed in the background of a specimen spiked with C. pneumoniae.
## Selected Analytic Studies
#### Limit of Detection
The analytical sensitivity or Limit of Detection (LoD) for Adenovirus was determined by testing limiting dilutions of quantified cultures with the modified FilmArray RP. LoD is defined as the lowest concentration at which the analyte is consistently detected (detection in ≥95% of samples tested). Simulated NPS sample matrix (cultured human cells in VTM) was spiked with Adenovirus and 20 replicates were tested at the estimated LoD concentration of 100 TCIDs5/mL for each of four respiratory serotypes (AdVC1, AdVC2. AdVE4 and AdVC6). Adenovirus was detected in all 20 replicates for each
{8}------------------------------------------------
serotype and the system LoD for Adenovirus was reduced from 300 TCID50/mL with the original panel to 100 TCID50/mL in the modified panel.
| Adenovirus<br>Serotype | Modified FilmArray RP | | | Original FilmArray RP |
|------------------------|-----------------------|------------|------------|------------------------------|
| | LoD<br>(TCID50/mL) | # Positive | % Positive | Estimated LoD<br>(TCID50/mL) |
| AdVC1 | 100 | 20/20 | 100.0% | 300 |
| AdVC2 | 100 | 20/20 | 100.0% | 30,000 |
| AdVE4 | 100 | 20/20 | 100.0% | 300 |
| AdVC6 | 100 | 20/20 | 100.0% | 3,000,000 |
The LoD for all other analytes detected by the FilmArray RP was found to be equivalent between the original and modified panels by testing replicate samples at LoD level as well as bracketing levels.
### Analytical Reactivity (Inclusivity)
The analytical reactivity of the modified FilmArray RP system was evaluated with an Adenovirus inclusivity panel representing 6 species (A-F) and 22 serotypes. These included both respiratory and non-respiratory adenovirus isolates. The modified FilmArray RP is designed to detect all respiratory species/serotypes of Adenovirus (B, C, and E). Detection of non-respiratory species (A, D, F and G) will vary. It is important to note that the presence of non-respiratory species of Adenovirus in clinical respiratory specimens is expected to be rare. Variable detection of these viruses by the FilmArray RP should have little to no impact on the clinical performance (sensitivity) of the system.
Samples were tested with both the original and modified panels at the Adenovirus LoD established for the modified panel (100 TCID50/mL). If an Adenovirus isolate was not detected by the modified panel at LoD, testing was repeated at 10x LoD (1.000 TCID30/mL). Testing above 10x LoD was not performed. Some reactivity with serotypes listed as Not Detected (ND) may be observed if present in a sample at high levels.
AdVB55 and AdVC57 are the only respiratory serotypes that were not evaluated for inclusivity. Available sequence information for these serotypes indicates a perfect match to FilmArray Adenovirus assay primers and efficient detection at 1x LoD is predicted.
| Species | Type | Isolate | Test Level | x<br>LoD | Original<br>FilmArray RP | Modified<br>FilmArray RP |
|---------|------|---------------------------|---------------|----------|--------------------------|--------------------------|
| B | 3 | Zeptometrix<br>#0810062CF | 100 TCID50/mL | 1 x | Detected | Detected |
| | 7a | Zeptometrix<br>#0810021CF | 100 TCID50/mL | 1 x | Detected | Detected |
| | 7d2 | lowa/2001 | 100 TCID50/mL | 1 x | Detected | Detected |
| | 7h | lowa/1999 | 100 TCID50/mL | 1 x | Detected | Detected |
Inclusivity Results for Adenovirus Respiratory Species/Serotypes Tested with the Original and Modified Film Array RP
{9}------------------------------------------------
| Species | Type | Isolate | Test Level | x LoD | Original<br>FilmArray RP | Modified<br>FilmArray RP |
|---------|------|-----------------------------|---------------|-------|--------------------------|--------------------------|
| | 11 | Wisconsin/2005 | 100 TCID50/mL | 1x | ND | Detected |
| | 14 | Missouri/2005 | 100 TCID50/mL | 1x | ND | Detected |
| | 16 | ATCC VR-17 | 100 TCID50/mL | 1x | Detected | Detected |
| | 21 | Missouri/2005 | 100 TCID50/mL | 1x | ND | Detected |
| | 34 | UIRF-Texas/2005 | 100 TCID50/mL | 1x | ND | Detected |
| | 35 | ATCC VR-718 | 100 TCID50/mL | 1x | ND | Detected |
| | 50 | ATCC VR-1602 | 100 TCID50/mL | 1x | ND | Detected |
| | 1 | Zeptometrix<br>#0810050CF | 100 TCID50/mL | 1x | Detected | Detecteda |
| | 2 | New York/2001 | 100 TCID50/mL | 1x | ND | Detected |
| | | ATCC VR-846 | 100 TCID50/mL | 1x | ND | Detected |
| | | Clinical isolate<br>#266153 | 100 TCID50/mL | 1x | ND | Detected |
| | | Clinical isolate<br>#266161 | 100 TCID50/mL | 1x | ND | Detected |
| C | | Clinical isolate<br>#266213 | 100 TCID50/mL | 1x | ND | Detected |
| | 5 | Zeptometrix<br>#0810020CF | 100 TCID50/mL | 1x | ND | Detected |
| | 6 | Colorado/2005 | 100 TCID50/mL | 1x | ND | Detected |
| | | ATCC VR-6 | 100 TCID50/mL | 1x | ND | Detected |
| | | Clinical isolate<br>#274924 | 100 TCID50/mL | 1x | ND | Detected |
| | | Clinical isolate<br>#274948 | 100 TCID50/mL | 1x | ND | Detected |
| | | Clinical isolate<br>#275032 | 100 TCID50/mL | 1x | ND | Detected |
| E | 4a | South<br>Carolina/2004 | 100 TCID50/mL | 1x | Detected | Detected |
| | 4p3 | New Jersey/2005 | 100 TCID50/mL | 1x | Detected | Detected |
* The initial test of AdVCI with the modified FilmArray RP pouch was invalid due to a control failure. Adenovirus was detected on the retest.
. ·
.
,
·
{10}------------------------------------------------
| Species | Type | Isolate | Test Level | x LoD | Original<br>FilmArray RP | Modified<br>FilmArray RP |
|---------|------|---------------------------|-----------------|-------|--------------------------|--------------------------|
| A | 12 | ATCC VR-863 | 1,000 TCID50/mL | 10x | ND | ND |
| | 18 | ATCC VR-19 | 1,000 TCID50/mL | 10x | ND | ND |
| | 31 | Zeptometrix<br>#0810073CF | 1,000 TCID50/mL | 10x | Detected | Detected |
| D | 8 | Zeptometrix<br>#0810069CF | 100 TCID50/mL | 1x | ND | Detected |
| | 20 | Zeptometrix<br>#0810115CF | 100 TCID50/mL | 1x | Detected | Detected |
| | 37 | Zeptometrix<br>#0810119CF | 100 TCID50/mL | 1x | Detected a | Detected |
| F | 40 | Zeptometrix<br>#0810084CF | 1,000 TCID50/mL | 10x | ND | ND |
| | 41 | Indiana/2004 | 100 TCID50/mL | 1x | Detected | Detected b |
Inclusivity Results for Non-Respiratory Adenovirus Species/Serotypes Tested with the Original and Modified FilmArray RP
4 The initial test of AdVD37 at 1x LoD in the original FilmArray RP pouch was negative. Adenovirus was detected on the retest. b The initial test of AdVF41 at 1x LoD in the modified FilmArray RP pouch was negative. Adenovirus was detected on the retest.
# Analytical Specificity (Cross-reactivity and Exclusivity)
The potential for cross-reactivity with organisms detected by the FilmArray RP was evaluated by testing simulated NPS samples containing high concentrations of respiratory panel viruses and bacteria (tens to thousands-fold higher than LoD) with the modified panel. No cross-reactivity was observed.
NOTE: Although not observed in this study, the Coronavirus OC43 assay may cross-react with certain strains of Coronavirus HKU1 when present in the sample at high concentrations.
| Analyte | Type / Strain / ID | Test Concentration | Multiple of<br>LoD Tested |
|--------------------------|--------------------------------|------------------------|---------------------------|
| Adenovirus | AdVC1 | 1.00E+05 TCID50/mL | 1,000x |
| Coronavirus | 229E<br>ATCC VR-740 | 5.67E+03 TCID50/mL | 1,418x |
| | HKU1<br>Clinical specimen | 1.34E+08 RNA copies/mL | 70 x |
| | NL63<br>NR-470 | 5.67E+03 TCID50/mL | 1,134x |
| | OC43<br>ATCC VR-759 | 7.30E+04 TCID50/mL | 122x |
| Human<br>Metapneumovirus | Type A1 - hMPV-16<br>IA10-2003 | 8.17E+03 TCID50/mL | 4,085x |
| Human Rhinovirus / | Echovirus 6 | 3.40E+06 TCID50/mL | 113x |
Results of Cross-reactivity Testing with the Modified FilmArray RP - RP Organisms
{11}------------------------------------------------
| Analyte | Type / Strain / ID | Test Concentration | Multiple of<br>LoD Tested |
|--------------------------------|---------------------|---------------------|---------------------------|
| Enterovirus | Rhinovirus 1A | 5.67E+03 TCID50/mL | 5,670x |
| Influenza A<br>H1N1 | A/Brisbane/59/07 | 1.00E+05 TCID50/mL | 500x |
| Influenza A<br>H1-2009 | A/SwineNY/03/2009 | 8.40E+05 TCID50/mL | 840x |
| Influenza A<br>H3N2 | A/Wisconsin/67/2005 | 8.17E+03 TCID50/mL | 1634x |
| Influenza B | B/FL/04/06 | 1.67E+04 TCID50/mL | 278x |
| Parainfluenza Virus | Type 1 | 1.39E+04 TCID50/mL | 28x |
| | Type 2 | 1.67E+04 TCID50/mL | 1,670x |
| | Type 3 | 1.00E+05 TCID50/mL | 10,000x |
| | Type 4a | 5.67E+03 TCID50/mLa | 1.13x |
| Respiratory<br>Syncytial Virus | Type A | 1.39E+04 TCID50/mL | 6,950x |
| Bordetella pertussis | A639 | 1.00E+06 CFU/mL | 250x |
| Chlamydophila<br>pneumoniae | TW183 | 2.42E+05 copies/mL | .81x |
| Mycoplasma<br>pneumoniae | M129 | 1.88E+05 TCID50/mL | 6,267x |
4 Highest test concentration possible based on the concentration of virus in the stock culture fluid.
The potential for the FilmArray RP system to cross-react with non-FilmArray RP organisms was evaluated by testing an exclusivity panel consisting of 26 bacteria, 6 viruses, and 1 yeast. These organisms were selected based on their relatedness to FilmArray RP organisms, clinical relevance (cause respiratory symptoms or represent nasopharyngeal flora), or high prevalence within the population (e.g. Herpes Simplex Virus). Negative sample matrix was spiked with bacteria or fungi at a concentration of 106 CFU/mL and viruses at a concentration between 104 - 105 TCID50/mL, or the highest concentration possible. The modified FilmArray RP system did not cross-react with the exclusivity panel organisms.
Results of Exclusivity Testing with the Modified FilmArray RP - Non-RP Organisms
| Virus | Strain / Isolate |
|--------------------------|-------------------------|
| Bocavirus | Clinical Specimen |
| Cytomegalovirus (CMV) | AD-169 (VR-538) |
| Epstein-Barr Virus (EBV) | B95-8 |
| Herpes Simplex Virus | Type 1 |
| Measles Virus | Edmonston |
| Mumps | Zeptometrix # 0810079CF |
| Yeast | Strain / Isolate |
| Candida albicans | Zeptometrix #0801504 |
| Bacterium | Strain / Isolate |
{12}------------------------------------------------
| Bordetella bronchiseptica | clinical isolate |
|----------------------------|----------------------|
| Bordetella holmesii | F061 |
| Bordetella parapertussis | A747 |
| Chlamydia trachomatis | D-UW3 |
| Corynebacterium diptheriae | ATCC14779 |
| Escherichia coli | O157:H7 |
| Haemophilus influenzae | MinnA |
| Lactobacillus acidophilus | Type strain |
| Lactobacillus plantarum | 17-5 |
| Legionella longbeacheae | Long Beach 4 |
| Legionella micdadei | Tatlock |
| Legionella pneumophilia | Philadelphia |
| Moraxella catarrhalis | Ne 11 (type strain) |
| Mycobacterium tuberculosis | H37Ra-1 |
| Mycoplasma hominis | ATCC 23114 |
| Mycoplasma genitalium | ATCC 33530 |
| Neisseria elongata | type strain |
| Neisseria gonorrhoeae | ATCC 700825 |
| Neisseria meningitidis | M1027 (type strain) |
| Pseudomonas aeruginosa | Zeptometrix #0801519 |
| Staphylococcus aureus | COL |
| Staphylococcus epidermidis | RP62A |
| Streptococcus pneumoniae | type 59 |
| Streptococcus pyogenes | Zeptometrix #0801512 |
| Streptococcus salivarius | ATCC 13419 |
| Ureaplasma urealyticum | ATCC 27618 |
:
.
·
.
. . . . .
. . . . . . . . . . . .
:
.
.
.
{13}------------------------------------------------
# Competitive Interference
Interference testing was performed by preparing simulated NPS samples with a combination of two respiratory viruses, with one being Adenovirus. The competing viruses were selected based on the dominant Adenovirus co-infections documented in the FilmArray RP Clinical Evaluation. In total, five different virus combinations (co-infections) were evaluated with each virus tested at a low level (LoD for organism) and at a high or competing level (~ 5,000 - 100,000 TCID50/mL).
The modified FilmArray RP demonstrated improved detection of Adenoviruses compared to detection in the original panel. This is consistent with the improved analytical sensitivity and reactivity for Adenovirus in the modified panel. There were no signs of interference or inaccurate results with competing organisms in a sample.
| Sample | LoD<br>Virus | Competing<br>Virus | Original FilmArray RP Result | Modified FilmArray RP Result |
|--------|--------------|--------------------|--------------------------------------------|--------------------------------------------|
| 1a | AdVCI | HRV | Adenovirus<br>Human Rhinovirus/Enterovirus | Adenovirus<br>Human Rhinovirus/Enterovirus |
| 1b | HRV | AdVC1 | Adenovirus<br>Human Rhinovirus/Enterovirus | Adenovirus<br>Human Rhinovirus/Enterovirus |
| 2a | AdVC5 | hMPV | Human Metapneumovirus | Adenovirus<br>Human Metapneumovirus |
| 2b | hMPV | AdVC5 | Adenovirus<br>Human Metapneumovirus | Adenovirus<br>Human Metapneumovirus |
| 3a | AdVC6 | RSV | -<br>Respiratory Syncytial Virus | Adenovirus<br>Respiratory Syncytial Virus |
| 3b | RSV | AdVC6 | -<br>Respiratory Syncytial Virus | Adenovirus<br>Respiratory Syncytial Virus |
| 4a | AdVB7h | AdVE4p3 | Adenovirus | Adenovirus |
| 4b | AdVE4p3 | AdVB7h | Adenovirus | Adenovirus |
| 5a | AdVC2 | AdVB21 | Adenovirus | Adenovirus |
| 5b | AdVB21 | AdVC2 | Adenovirus | Adenovirus |
#### Results for Adenovirus Co-infection Samples Tested with the Original and Modified FilmArray RP
{14}------------------------------------------------
#### DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/14/Picture/1 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a stylized caduceus symbol, which is a staff with two snakes coiled around it, and the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged in a circular pattern around the symbol. The text is in all caps and is in a sans-serif font. The logo is black and white.
#### Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-002
FEB 1 1 2013
BioFire Diagnostics, Inc. C/O Beth Lingenfelter, M.S. 390 Wakara Way Salt Lake City, UT 84108
Re: k123620 Trade/Device Name: FilmArray® Respiratory Panel (RP) Regulation Number: 21 CFR 866.3980 Regulation Name: Respiratory Viral Panel Multiplex Nucleic Acid Assay Regulatory Class: Class II Product Code: OCC, OEM, OOU, OEP, OTG, OQW, OOI, OZZ, OZY, OZX Dated: November 21, 2012 Received: November 23, 2012
Dear Ms. Lingenfelter:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
{15}------------------------------------------------
If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostics and Radiological Health at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket 5 150. Thise, prease now as a more of any of any of a reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
under the MDA rogalation (21 Of 11 are et Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Tou may of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours,
# Sally A. Hojvat
Sally Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
{16}------------------------------------------------
# Indications for Use
# 510(k) Number (if known): K123620 Device Name: FilmArray® Respiratory Panel (RP)
FilmArray® Respiratory Panel (RP) is a multiplexed nucleic acid test intended for use with the FilmArray Instrument for the simultaneous qualitative detection and identification of multiple respiratory viral and bacterial nucleic acids in nasopharyngeal swabs (NPS) obtained from individuals suspected of respiratory tract infections. The following organism types and subtypes are identified using the FilmArray RP: Adenovirus, Coronavirus 229E, Coronavirus HKU1, Coronavirus NL63, Coronavirus OC43, Human Metapneumovirus, Influenza A, Influenza A subtype H1, Influenza A subtype H3, Influenza A subtype H1-2009, Influenza B, Parainfluenza Virus 1, Parainfluenza Virus 2, Parainfluenza Virus 3, Parainfluenza Virus 4, Human Rhinovirus/Enterovirus, Respiratory Syncytial Virus, Bordetella pertussis, Chlamydophila pneumoniae, and Mycoplasma pneumoniae. The detection and identification of specific viral and bacterial nucleic acids from individuals exhibiting signs and symptoms of a respiratory infection aids in the diagnosis of respiratory infection if used in conjunction with other clinical and epidemiological information. The results of this test should not be used as the sole basis for diagnosis, treatment, or other management decisions. Negative results in the setting of a respiratory illness may be due to infection with pathogens that are not detected by this test or, lower respiratory tract infection that is not detected by a nasopharyngeal swab specimen. Positive results do not rule out co-infection with other organisms: the agent(s) detected by the FilmArray RP may not be the definite cause of disease. Additional laboratory testing (e.g. bacterial and viral culture, immunofluorescence, and radiography) may be necessary when evaluating a patient with possible respiratory tract infection.
Due to the small number of positive specimens collected for certain organisms during the prospective clinical study, performance characteristics for Bordetella pertussis, Coronavirus 229E. Coronavirus OC43, Influenza A H1, Influenza A H3, Influenza A H1-2009, Influenza B, Mycoplasma pneumoniae, Parainfluenza Virus 1, Parainfluenza Virus 2, and Parainfluenza Virus 4 were established primarily with retrospective clinical specimens. Performance characteristics for Chlamydophila pneumoniae were established primarily using contrived clinical specimens.
Due to the genetic similarity between Human Rhinovirus and Enterovirus, the FilmArray RP cannot reliably differentiate them. A positive FilmArray RP Rhinovirus/Enterovirus result should be followed-up using an alternate method (e.g., cell culture or sequence analysis).
The FilmArray RP assay for Coronavirus OC43 may cross-react with some isolates of Coronavirus HKU1. A dual positive result may be due to cross-reactivity or may indicate a coinfection.
{17}------------------------------------------------
Performance characteristics for Influenza A were established when Influenza A H1-2009, A H1, and A H3 were the predominant Influenza A viruses in circulation. Performance of detecting Influenza A may vary if other Influenza A strains are circulating or a novel Influenza A virus emerges. If infection with a novel Influenza A virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent Influenza viruses and sent to state or local health departments for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.
Prescription Use _ × (Part 21 CFR 801 Subpart D)
AND/OR
Over-the-Counter Use __ (21 CFR 801 Subpart C)
# (PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostics and Radiological Health (OIR)
Tawna Feldbak
123620
Office of In Vitro Diagnostics and Radiological Health
న్నారు. విశ్రీ న
